Biotechnology products cover an increased proportion of all therapeutic drugs, including monoclonal antibodies, vaccines, growth factors, hormones, cytokines, coagulation factors, fusion proteins, enzymes and other proteins. Other than monoclonal antibodies and vaccines, many on this list possess a molecular mass below 50 kDa and a short terminal half-life that is in the range of minutes to hours.
The efficacy of protein therapeutics is strongly determined by their pharmacokinetic properties, including their plasma half-lives, which influence distribution and excretion. Although a small size facilitates tissue penetration, these molecules are often rapidly cleared from circulation. Thus, to maintain a therapeutically effective concentration over a prolonged period of time, infusions or frequent administrations are performed, or the drug is applied loco—regional or subcutaneously utilizing a slow adsorption into the blood stream. These limitations of small size protein drugs have led to the development and implementation of half-life extension strategies to prolong circulation of these recombinant antibodies in the blood and thus improve administration and pharmacokinetic as well as pharmacodynamic properties.
The present invention employs such a strategy in order to increase the hydrodynamic size or volume of proteins of interest or fragments thereof, including peptides, by a particular factor and thereby improve administration, pharmacokinetics as well as pharmacodynamic properties of the same. This increase in hydrodynamic volume is achieved by making use of a peptide-based technology for extending serum half-life of proteins and peptides. This technology is based on using a natural peptide, the C-terminal peptide (CTP) of the beta chain of human chorionic gonadotropin (hCG), which provides hCG with the required longevity to maintain pregnancy. The beta chain of luteinizing hormone (LH), a fertility hormone that triggers ovulation, is almost identical to hCG but does not include the CTP. As a result, LH has a significantly shorter half-life in blood. Attaching a predetermined number of CTPs to a protein or peptide of interest increases the hydrodynamic volume of the same by a specific factor and results in improved properties that include an enhanced serum half-life and potency of the protein or peptide of interest.